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CORD-19:c738a511a9c18e7e831b40f1ec3605fe4cdeb6d1 JSONTXT 7 Projects

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Id Subject Object Predicate Lexical cue
T1 0-345 Sentence denotes Journal Pre-proof Breast radiotherapy under COVID-19 pandemic resource constraints --approaches to defer or shorten treatment from a Comprehensive Cancer Center in the United States Breast radiotherapy under COVID-19 pandemic resource constraints --approaches to defer or shorten treatment from a Comprehensive Cancer Center in the United States
T2 347-355 Sentence denotes Abstract
T3 356-476 Sentence denotes Breast radiotherapy accounts for a significant proportion of patient volume in contemporary radiation oncology practice.
T4 477-725 Sentence denotes In the setting of anticipated resource constraints and widespread community infection with SARS-CoV-2 during the COVID-19 pandemic, measures for balancing both infectious and oncologic risk among patients and providers must be carefully considered.
T5 726-921 Sentence denotes Here, we present evidence-based guidelines for omitting or abbreviating breast cancer radiotherapy, where appropriate, in an effort to mitigate risk to patients and optimize resource utilization.
T6 923-1043 Sentence denotes Breast radiotherapy accounts for a significant proportion of patient volume in contemporary radiation oncology practice.
T7 1044-1292 Sentence denotes In the setting of anticipated resource constraints and widespread community infection with SARS-CoV-2 during the COVID-19 pandemic, measures for balancing both infectious and oncologic risk among patients and providers must be carefully considered.
T8 1293-1488 Sentence denotes Here, we present evidence-based guidelines for omitting or abbreviating breast cancer radiotherapy, where appropriate, in an effort to mitigate risk to patients and optimize resource utilization.
T9 1489-1804 Sentence denotes Multidisciplinary breast cancer experts at a high-volume comprehensive cancer center convened contingency planning meetings over the early days of the COVID-19 pandemic to review the relevant literature and establish recommendations for the application of hypofractionated and abbreviated breast radiation regimens.
T10 1805-1987 Sentence denotes Substantial evidence exists to support omitting radiation among certain favorable risk subgroups of breast cancer patients and for abbreviating or accelerating regimens among others.
T11 1988-2219 Sentence denotes For those who require either whole-breast or post-mastectomy radiation, with or without coverage of the regional lymph nodes, a growing body of literature supports various hypofractionated approaches that appear safe and effective.
T12 2220-2507 Sentence denotes In the setting of a public health emergency with the potential to strain critical healthcare resources and place patients at infection risk, the parsimonious application of breast radiotherapy may alleviate a significant clinical burden without compromising long term oncologic outcomes.
T13 2508-2658 Sentence denotes The judicious and personalized use of immature study data may be warranted in the setting of a competing mortality risk from this widespread pandemic.
T14 2659-2873 Sentence denotes Breast radiotherapy (RT) is a curative component of treatment for many breast cancer presentations, albeit with limited locoregional benefit for certain patients and no survival implications for others (e.g. DCIS).
T15 2874-3078 Sentence denotes 1 In the setting of the COVID-19 pandemic in which community infection represents a mortal risk, the anticipated benefit of breast RT in certain settings must be carefully weighed against infectious risk.
T16 3079-3340 Sentence denotes Whereas breast cancer represents the most common non-cutaneous malignancy in the United States, limiting the overall use and duration of breast RT under conditions of extreme resource constraints is prudent and may significantly alleviate institutional burdens.
T17 3341-3605 Sentence denotes Guidance from the US Centers for Disease Control and World Health Organization advise limiting the sorts of person-to-person interactions that are likely to occur in clinical spaces among patients and healthcare staff during prolonged daily fractionation regimens.
T18 3606-3763 Sentence denotes In addition, healthcare resources in many settings may need to be repurposed for pandemic management such that limiting utilization is of renewed importance.
T19 3764-3956 Sentence denotes Therefore, abbreviated fractionation regimens with nascent feasibility literature, as presented below, should be more strongly considered than under typically-conservative practice conditions.
T20 3957-4339 Sentence denotes A team of radiation oncologists that specialize in breast cancer management at our comprehensive cancer center convened multi-disciplinary and cross-institutional contingency planning meetings over the early days of the COVID-19 pandemic to review the relevant literature and establish recommendations for the safe application of hypofractionated and abbreviated radiation regimens.
T21 4340-4524 Sentence denotes The literature was reviewed with an emphasis on randomized controlled trial and level one evidence, followed by prospective observational studies, systematic reviews and meta-analyses.
T22 4525-4617 Sentence denotes In general, the omission of radiotherapy among those who are eligible should be prioritized.
T23 4618-4821 Sentence denotes These subgroups of low-risk patients have been studied in landmark trials demonstrating a moderate local control benefit of RT without improvement in already-excellent disease-specific survival outcomes.
T24 4822-4849 Sentence denotes • Ductal carcinoma in situ:
T25 4850-5021 Sentence denotes Prospective observational studies 2 and randomized controlled trials 3 have reproducibly demonstrated a lack of survival benefit for RT among favorable DCIS presentations.
T26 5022-5196 Sentence denotes It is, therefore, advisable to forego RT for those with mammographically-detected lesions <2.5cm in size, of low-or intermediate-grade, with adequate >=2mm resection margins.
T27 5197-5270 Sentence denotes 4 Caution is warranted if foregoing RT in patients under 40 years of age.
T28 5271-5294 Sentence denotes 5,6 • Invasive disease:
T29 5295-5576 Sentence denotes The omission of RT is preferred among those age 70 years and older who have estrogen-receptor positive (ER+) tumors that are <=3cm in size with no involved nodes (pT1-2N0M0), negative resection margins (i.e. "no tumor on ink" 7 ), and who are eligible to receive endocrine therapy.
T30 5577-5681 Sentence denotes 8 A large study with limited follow-up suggests lowering this threshold to 65 years of age is also safe.
T31 5682-5933 Sentence denotes 9 For patients younger than 65 years of age, ongoing studies demonstrate equipoise with regard to those who have biomarker-low disease that otherwise fits the above clinicopathologic parameters, but no mature data exist in this domain [10] [11] [12] .
T32 5934-5946 Sentence denotes Delaying RT:
T33 5947-6086 Sentence denotes Uncertainty surrounding the current public health emergency has made predictions about future resource allocation particularly challenging.
T34 6087-6158 Sentence denotes Estimates of population-level relief range from weeks to over one-year.
T35 6159-6317 Sentence denotes 13, 14 In the interest of alleviating current workload and resource constraints, evidence exists to support delaying RT among certain populations, as follows:
T36 6318-6345 Sentence denotes • Ductal carcinoma in situ:
T37 6346-6464 Sentence denotes In patients requiring RT for DCIS, radiation can be safely delayed up to 12 weeks following breast conserving surgery.
T38 6465-6487 Sentence denotes 15 • Invasive disease:
T39 6488-6771 Sentence denotes Patients with early-stage, node-negative, ER+ breast cancer can safely begin radiotherapy 8-12 weeks after breast conserving surgery without compromising disease control or survival, with several large studies showing that a delay up to 20 weeks may be safe in an appropriate subset.
T40 6772-6913 Sentence denotes 16, 17 There is limited evidence to guide the interval from chemotherapy to RT, and most trials initiate RT 4-6 weeks following chemotherapy.
T41 6914-7049 Sentence denotes Extrapolation from the surgical literature above suggests that an interval of up to 12 weeks from chemotherapy to RT may be reasonable.
T42 7050-7255 Sentence denotes For patients with ER+ breast cancers, either DCIS or invasive, who may otherwise experience a delay or interruption in treatment, we support the prompt initiation of endocrine therapy among those eligible.
T43 7256-7428 Sentence denotes There is no evidence to suggest inferior local control or survival with concurrent hormonal therapy and radiation, including both tamoxifen 18, 19 and aromatase inhibitors.
T44 7429-7609 Sentence denotes 20 Though subtle differences in breast edema, fibrosis/cosmesis, and lung toxicity have been reported, the overall evidence is mixed and should not limit use of concurrent therapy.
T45 7610-7659 Sentence denotes 21 Accelerated partial breast irradiation (APBI):
T46 7660-7821 Sentence denotes A large body of literature, including several landmark prospective trials, has established the safety and efficacy of APBI among appropriately selected patients.
T47 7822-8069 Sentence denotes This paradigm is based on the historical observation that most recurrences occur proximate to the tumor cavity, such that treatment of the tumor bed with a margin has now been shown to confer outcomes similar to whole-breast RT in select settings.
T48 8070-8257 Sentence denotes Moreover, utilization of a smaller target volume allows for acceleration of the overall regimen from 3-6 weeks down to 1-2 weeks -a critical gain under resource constrained circumstances.
T49 8258-8424 Sentence denotes Additional benefits may include reduced acute toxicity as evidenced by ten-year follow-up of the Florence regimen (30Gy in 5 fractions, administered every-other-day).
T50 8425-8517 Sentence denotes 22 Various techniques and fractionation regimens are available for partial breast radiation.
T51 8518-8671 Sentence denotes The use of brachytherapy is discouraged in the setting of strain on hospital resources, also yielding increased opportunities for exposure and infection.
T52 8672-8855 Sentence denotes Accelerated external beam PBI regimens using 3D-CRT now have a large body of evidence supporting their use, with 38.5Gy in 10 fractions delivered twice-daily as a well-studied scheme.
T53 8856-8996 Sentence denotes In one report, cosmesis appeared to score worse with this regimen 23 , while in the seminal US study, this appeared to be less of a concern.
T54 8997-9221 Sentence denotes 24 Other well-established options for APBI include 40Gy in 10 fractions daily using 3D-CRT 25, 26 , and 30Gy in 5 fractions every-other-day using IMRT 22 (daily fractionation appears well-tolerated; personal correspondence).
T55 9222-9365 Sentence denotes Meanwhile, 40Gy in 15 daily fractions to the partial breast is also an effective regimen, though is more prolonged than the other APBI options.
T56 9366-9686 Sentence denotes 27 ASTRO consensus guidelines 28 and UK 29 have identified a population for which there is reasonable agreement regarding suitability of APBI: patients 50 years of age or older with screen-detected invasive disease that is <=2cm in size, ER+ and node negative, or DCIS that is low/intermediate grade and <=2.5cm in size.
T57 9687-9850 Sentence denotes Of note, NSABP-B39 also included 800 patients with ER-breast cancer who exhibited excellent local control, suggesting that APBI may be reasonable among this group.
T58 9851-10000 Sentence denotes Among patients who require whole-breast RT without nodal treatment, hypofractionation is the preferred standard of care in the United States 30, 31 .
T59 10001-10098 Sentence denotes To that end, a number of fractionation schemes are well-supported by randomized trials including:
T60 10099-10155 Sentence denotes 42.56Gy in 16 fractions 32 and 40Gy in 15 fractions 33 .
T61 10156-10331 Sentence denotes Data is emerging for more extreme hypofractionation supporting 28.5Gy in 5 once-weekly fractions 34 , as well as a more accelerated daily regimen of 26Gy in 5 daily fractions.
T62 10332-10516 Sentence denotes 35 Though long-term local recurrence data have not yet resulted for FAST Forward, 3year normal tissue toxicity appears equivalent to the well-tolerated three-week fractionation scheme.
T63 10517-10888 Sentence denotes While various concerns have slowed widespread adoption of shorter regimens for whole-breast radiation, a number of prospective phase II, single arm and retrospective series have demonstrated efficacy and safety among groups that were previously thought to be of particular concern including: high grade tumors 36 , DCIS 37 , young age 38 or triple-negative breast cancer.
T64 10889-10948 Sentence denotes 36 Post-mastectomy and/or Regional Nodal Irradiation (RNI):
T65 10949-11183 Sentence denotes Analyses of the two landmark studies, MA.20 and EORTC 22922, reproducibly demonstrated that RNI reduces distant recurrence risk and significantly improves disease-free-survival, even among those with a limited axillary disease burden.
T66 11184-11325 Sentence denotes 39, 40 As a result, an increasing number of patients have become eligible to receive comprehensive RNI following breast conservation or PMRT.
T67 11326-11844 Sentence denotes Unfortunately, hypofractionated nodal irradiation has yet to see widespread adoption in the United States, although a nascent literature does suggest it is safe to employ 40 Gy in 15 daily fractions targeting the breast/chest wall and regional nodes (presuming the supraclavicular hotspot is below 105%; otherwise 39Gy in 15 fractions is preferred) 33, [41] [42] [43] , with ongoing studies utilizing this regimen in a randomized fashion to suggest true clinical equipoise (RT-CHARM: NCT03414970; FABREC: NCT03422103).
T68 11845-12000 Sentence denotes The UK FAST FORWARD trial includes a 5fraction lymphatic RT cohort, but this is not yet considered safe outside of a trial or in the setting of palliation.
T69 12001-12072 Sentence denotes Boost radiotherapy has more limited applications in emergency settings.
T70 12073-12100 Sentence denotes • Ductal carcinoma in situ:
T71 12101-12251 Sentence denotes The largest study to date evaluating the benefit of a boost in the setting of DCIS found a <2% local control benefit following whole breast radiation.
T72 12252-12380 Sentence denotes 44 Given the absence of a survival benefit, boost can be omitted in resource-constrained settings, as was standard on RTOG 9804.
T73 12381-12534 Sentence denotes 3 However, as above, caution is warranted among those younger than 40 years of ages in whom boost was shown to improve local control by 10% at 72 months.
T74 12535-12557 Sentence denotes 45 • Invasive disease:
T75 12558-12757 Sentence denotes Following whole breast radiation, a tumor bed boost should be considered only in the presence of significant local recurrence risk factors: ≤60 years of age, high grade tumors, or inadequate margins.
T76 12758-12948 Sentence denotes 46 A standard boost after hypofractionated whole breast radiation involves 4-6 fractions, although evidence suggests that a simultaneous integrated boost may be similarly safe and effective.
T77 12949-13212 Sentence denotes 47, 48 In the setting of ultra-hypofractionation with 5-fraction regimens, it is reasonable to consider a single 5.2Gy dose to the tumor bed (personal correspondence), although this fractional boost dose remains to be reported beyond the brachytherapy literature.
T78 13213-13341 Sentence denotes 49 For patients receiving whole breast and nodal irradiation, a simultaneous integrated boost (SIB) can reduce treatment visits.
T79 13342-13474 Sentence denotes This can be achieved with IMRT or VMAT, but is also possible with a supplemental electron field delivered with each 3D-CRT fraction.
T80 13475-13601 Sentence denotes Under extreme circumstances, it may be necessary to prioritize which breast cancer patients can receive radiotherapy services.
T81 13602-13699 Sentence denotes Prioritization of patients for whom RT is anticipated to provide a survival benefit is paramount.
T82 13700-13818 Sentence denotes Based on available evidence and nascent clinical judgement, we have defined tiers of elevated priority (see Table 2 ).
T83 13819-13989 Sentence denotes Of note, prioritization within each tier is left to the treating physicians' discretion based on patient age, comorbidities, risk of exposure and predicted benefit of RT.
T84 13990-14291 Sentence denotes As governments restrict public movement to limit continued spread of the SARS-CoV-2 pandemic, radiation oncologists must now make an unprecedented calculus on behalf of our patients: the mortal risk of presenting for treatment and being exposed to infection, versus the benefit of radiotherapy itself.
T85 14292-14622 Sentence denotes It therefore behooves us to consider 1) omitting radiotherapy when appropriate, 2) delaying radiation while initiating endocrine therapy in low-risk patients with ER+ breast cancer, and 3) rapidly adopting accelerated schemes when possible in a concerted effort to protect our communities and conserve scarce healthcare resources.
T86 14623-14845 Sentence denotes For illustrative case presentations and guidance in contouring and planning the various regimens described above including target volumes, organs at risk, and relevant expansions, please visit http://econtour.org/hypofrac.
T87 14846-14954 Sentence denotes Online cases also include dosimetric guidance and the dose constraints used in various supportive protocols.
T88 14955-15177 Sentence denotes For illustrative case presentations and guidance in contouring and planning the various regimens described above including target volumes, organs at risk, and relevant expansions, please visit http://econtour.org/hypofrac.
T89 15178-15322 Sentence denotes Online cases also include dosimetric guidance and the dose constraints used in various supportive protocols. • ER+ with 1-3 positive nodes (N1a)
T90 15323-15342 Sentence denotes • Path N0 after NAC
T91 15343-15354 Sentence denotes • LVI (NOS)
T92 15355-15375 Sentence denotes • Node negative TNBC
T93 15376-15404 Sentence denotes (low priority for breast RT)
T94 15405-15448 Sentence denotes • Early-stage ER+ breast cancer (esp older)
T95 15449-15455 Sentence denotes • DCIS
T96 15456-15502 Sentence denotes • Otherwise not meeting criteria for Tiers 1-2
T97 15503-15517 Sentence denotes Abbreviations:
T98 15518-15618 Sentence denotes Neoadjuvant chemotherapy (NAC), triple negative breast cancer (TNBC), lymphovascular invasion (LVI).